A few weeks ago I wrote a piece discussing options for smoking cessation, and I specifically plugged varenicline, known as Chantix in most countries, as being perhaps the most effective tool we doctors can now offer. Since my posting, a few drug warnings have come out, and it begs the question: do the benefits still outweigh the risks? I say yes — I would still recommend for most people, but first let’s look into the new data.

The FDA recently added a box warning on the packaging, discussing varenicline’s increased risk of serious psychiatric symptoms. This June, there were some new warnings from the US FDA that taking Chantix slightly increases risks for heart attacks. And just last week comes a larger study which confirms this risk. More specifically (from the NY Times article):

The new study, known as a meta-analysis, compiled data from 14 random, blinded, placebo-controlled clinical trials that tracked cardiovascular outcomes. It found 52 out of 4,908 people taking Chantix had serious cardiovascular events, a rate of 1.06 percent, compared with 27 out of 3,308 people taking a placebo, a rate of 0.82 percent. While the absolute difference is only 0.24 percent, the weighted, relative difference is 72 percent.

Here’s another way to look at it: “doctors could expect to get one extra cardiac event associated with Chantix for every 28 smokers they treated with the drug. The researchers also estimated one additional person would quit for every 10 treated with Chantix.”

What About The Side Effects of Not Stopping Smoking?

So there’s the hard data: 0.82% of the placebo group had an event, and 1.06% of the Chantix users had an event. This is the data we docs need to be telling patients. Honestly, I find the absolute difference of an increased 0.24% to be very small, and if I were a smoker I would take the chance. After all, what about the “side effects” of not stopping smoking? Smoking itself is one of the major causes of heart disease! Not to mention all the deaths from lung cancers, chronic emphysema and other cancers. Let’s compare that absolute risk of 0.24% versus the facts of smoking:

• A smoker’s cumulative risk of dying from lung cancer before age 85 years was 22.1% for a male smoker and 11.9% for a female current smoker, in the absence of competing causes of death. For nonsmokers: a 1.1% probability (men) of European descent, and 0.8% in women. (source)
• Smokers under 40 are five times more likely to have a heart attack. (source)
• Male and female smokers lose an average of 13.4 to 14.3 years of life, respectively (source)

Let’s repeat that, in a way I would say to my mostly male smokers:

“You have a 0.24% absolute risk of a cardiovascular event on this medicine. You have a 22% risk of dying from lung cancer from continuing smoking. You decide.”

Even the FDA tries to keep the risks in perspective:

Smoking is an independent and major risk factor for cardiovascular disease, and smoking cessation is of particular importance in this patient population. The known benefits of Chantix should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease.

If my patient were a pack-a-day smoker for 30 years and wanted to quit, I still would recommend Chantix to them if they had no major psychiatric history. But this issue is now hotly debated among doctors, many of whom indeed want this drug pulled off the market. The excellent cardiovascular blog theheart.org has a nice review of this week’s controversy, including some of these highlights:

…In an accompanying editorial, Dr Taylor Hays (Mayo Clinic, Rochester, MN), who has been involved in clinical trials of varenicline, writes: “Although these results suggest a measure of caution should be taken in prescribing varenicline for tobacco dependence treatment, the small absolute risk of cardiovascular events associated with varenicline treatment is outweighed by the enormous benefit for reducing cardiovascular morbidity and mortality that can be achieved with successful smoking abstinence.”

Independent observer Dr Robert Bonow (Northwestern University, Chicago, IL) tended to side with Hays. He commented to heartwire: “The effects of smoking are so horrific that the benefits of stopping outweigh the risks of this drug in my view.”…

…Singh notes that while 1 in 10 people on Chantix quit smoking, the number needed to harm is 28. “There is not a great difference there.” He added: “We don’t know if the cardiovascular risk with Chantix stops after the drug has been discontinued. We have only looked at one-year’s data—when the patients were actually taking the drug. And we showed a 72% increased risk of cardiovascular events. We don’t know what happens later on.” He also noted that the actual cardiovascular risk with Chantix may be even greater as more people in the Chantix arm stopped smoking and so should have had an immediate reduction in risk.

“We all know the harms of smoking, and I am not disputing the need to quit. But I would advocate using a different method to help you quit. There are lots of other aids out there that work without increasing cardiovascular risk.”

Furberg reinforces this view. He commented to heartwire: “Quitting smoking is exceedingly important. If Chantix was very effective at getting people to quit smoking, you might argue in favor of its continued use, but it is only modestly effective. With Chantix, for every 10 people who take it, 9 have relapsed after a year. And we don’t know what happens to the 10th person after a year. So the efficacy is weak. And the adverse events are piling up.”…

My bottom line: smoking is a terrible disease and worldwide killer, and I still think varenicline is a very useful tool to get people to quit — although the side effects are more serious than we previously thought, and each patient needs to make their own decision.